Alzheimer's disease is a progressive neurodegenerative disorder which causes irreversible damage to brain cells leading to dementia and ultimately death. It is characterized by formation of amyloid plaques and neurofibrillary tangles in the brain. Currently, it is primarily diagnosed by exclusion of other known causes of dementia. Diagnosis at an early stage prior to irreversible changes is practically non-existent.
In order for therapeutic intervention to be significantly effective in treating Alzheimer's disease, it will have to be administered very early on prior to such irreversible changes. Accordingly, a biological marker which could flag patients who have a propensity or predisposition to developing Alzheimer's disease and thus could be a guide to early diagnosis would be a most-welcomed addition to the diagnostician's armamentarium.
Butyrylcholinesterase (BChE) (located on chromosome 3) is expressed in most human tissues (1), yet its function is unknown. BChE activity in the brain increases with age over 60 years and is elevated in Alzheimer's disease (AD) (2,3). Histochemically reactive BChE is associated with amyloid plaques and neurofibrillary tangles and with amyloid angiopathy in AD (4-8).
A large number of human genetic variants of BChE are known, two of the more common variants being the atypical allele (referred to as the A variant) and the K variant (BCHE-K). The A variant has an Asp70Gly mutation and is rare (0.5% allelic frequency), while the K variant has a point mutation at nucleotide 1615 (GCA.fwdarw.ACA) which changes alanine 539 to threonine and the catalytic activity is reduced by a third (9). BCHE-K is thought to have an allelic frequency of around 12% in Caucasians (9-11).
Until now, there has not been any known connection or association of AD with either the A variant or the K variant.
That the gene for apolipoprotein E4 (APOE .di-elect cons.4 allele) is a risk factor for AD is well established (12, 13). In fact, the likelihood of a carrier of APOE .di-elect cons.4 allele developing AD is 7-fold greater than a control who does not carry such gene.